Open Randomized Controlled Trial to Evaluate the Efficacy and Safety of Remifentanil Versus Nitrous Oxide in External Cephalic Version at Term in Singleton Pregnancy in Breech Presentation

Pregnancy Complications Clinical Trial

— REMIVER  

Official title:

Open Randomized Controlled Trial to Evaluate the Efficacy and Safety of Remifentanil Versus Nitrous Oxide in External Cephalic Version at Term in Singleton Pregnancy in Breech Presentation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01735669
• Other study ID #: REMIVER
• Status: Completed
• Phase: Phase 3
• First received: November 20, 2012
• Last updated: February 14, 2015
• Start date: July 2012
• Est. completion date: January 2014

Study information

• Verified date: February 2015
• Source: Hospital de Cruces
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

Objectives: The objective is to demonstrate the superiority of remifentanil versus nitrous oxide as adjuvant analgesic treatment to increase the chances of success of external cephalic version in the management of non-cephalic presentation in women with singleton pregnancy at term. Another objective is to compare their safety, tolerability and acceptability.

Methodology: single-center clinical trial, randomized, open, parallel-group and sequential design, with active comparator. Pragmatic approach. Sequential design of O'Brien-Fleming with two interim analysis. Analysis by intention to treat. Comparison of the rate of successful version, referred to analgesic effect, safety, caesarean rates and acceptability rate of the procedure for pregnant women.

Description:

External cephalic version is a procedure with clear benefits, but its realization is painful for the patient. Studies have shown that this pain limits external cephalic version efforts and therefore it negatively influences its success rate. In addition, any painful procedure has worse acceptance by patients so that its implementation is slow and not always universal. In this context, measures to reduce this pain could improve the success rate and acceptance of the procedure. All studies that have focused on reducing pain in external cephalic version have been made with regional anaesthetic techniques, epidural or spinal analgesia. Given the heterogeneity and the small number of studies there is still no conclusive data to make recommendations for regional anaesthesia in the external cephalic version. The introduction of regional anaesthesia can bring benefits to the version but it is not without drawbacks. This is an invasive anaesthetic technique that can reduce the security of the procedure and lead to longer hospital stay for the patient by the blockade that produces in the lower extremities. This in turn is associated with increased discomfort and costs of the procedure.

Cruces University Hospital has wide experience in carrying out external cephalic version procedures, being one of Spanish leading hospitals in terms of number of procedures and success rate. Currently external cephalic version procedures include analgesic support using nitrous oxide due to the combination of moderate analgesic activity and substantial ease of use.

The investigators belief is that the use of an opioid with advantageous pharmacokinetic properties and powerful analgesic effect as an adjunctive therapy during the course of external cephalic version procedures may become an efficacious and safe alternative, leading to increased pain relief and improved external cephalic version success rates. Its use requires, however, specific personnel and organizational facilities such as access to anesthetic support that can impede its widespread use. Therefore, the investigators is committed to explore feasibility and practical implementation factors as well as comparative efficacy and safety of this approach in non-cephalic presentation.

The investigators conducted a study to evaluate the effect of nitrous oxide as an adjunctive to external cephalic version and we observed a slight decrease in patient reported pain (visual analogous scale), with no effect on the rate of success. Currently, in the protocol of Cruces University Hospital the administration of nitrous oxide during the manoeuvres of the external cephalic version is routine practice. The investigators consider that the analgesic remifentanil is a better option for the external cephalic version than nitrous oxide by the combination of rapid onset of effect, with analgesic potency similar to regional anaesthesia and rapid metabolism that prevents their accumulation in tissues.

The lack of existing evidence on this issue, hence, prompts the investigators to conduct this pilot clinical trial aimed to assess scientific as well as logistical aspects involved in the performance of external cephalic version in non-cephalic presentation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. pregnancy at term (= 37 weeks)

2. singleton foetus in non-cephalic presentation

3. correct foetal cardiotocographic record

4. obstetrical ultrasound examination without findings of serious foetal malformations

5. indication for the performance of ECV

6. acceptance of ECV

7. age = 18 years

8. signature of informed consent

Exclusion Criteria:

1. previous version in the same pregnancy (previous ECV in a different pregnancy allowed)

2. contraindications to ECV: 1-placenta praevia, 2- placental abruption, 3-oligohydramnios (SPD <2), 4-foetal compromise 5-foetal death, 6-severe malformations, 7-multiple pregnancy, 8- Rh sensitization, 9- uterine abnormalities, 10- clotting disorders;

3. contraindications to Nitrous Oxide: 1-patients who require pure oxygen ventilation 2- intracranial hypertension 3- disorders of consciousness that impede the cooperation of the patient, 4-pneumothorax; 5-emphysematous bulla, 6-pulmonary embolism; 7-immersion accident, 8-bloating abdominal trauma 9- facial trauma that affects the area of application of the mask,10- patients who received the type gases SF6, C3F8, C2F6 (used in eye surgery), at least in the previous three months.

4. contraindications for remifentanil: hypersensitivity to remifentanil, fentanyl or fentanyl analogs or to any component of its formulation (according to technical requirements by manufacturer).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breech Presentation
• Complications; Cesarean Section
• Fetus or Neonate Affected by External Version Before Labor
• Inhalation of Nitrous Oxide
• Non-cephalic Presentation
• Pregnancy Complications

Intervention

Drug:
• Remifentanil

• Nitrous Oxide

Locations

Country	Name	City	State
Spain	Hospital Universitario Cruces	Barakaldo	Bizkaia

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Cruces

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success rate of ECV in singleton pregnancies in breech presentation at term		5 minutes	No
Secondary	Rate of adverse events and severity	Metrics (analysis)	30 days	Yes
Secondary	Pain Scores on the Visual Analog Scale	Metrics (scale)	60 min	No
Secondary	Rate of non-cephalic presentation in the delivery	Metrics (analysis)	30 days	No
Secondary	Caesarean rate	Metrics (analysis)	30 days	No
Secondary	Rate of women who would recommend the procedure	Metrics (questionnaire)	60 min	No
Secondary	Rate of women who would repeat the procedure	Metrics (questionnaire)	60 min	No
Secondary	Influence of the analgesia in the rate of women who would repeat the procedure	Metrics (questionnaire)	60 min	No
Secondary	Influence of the analgesia in the rate of women who would recommend the procedure	Metrics (questionnaire)	60 min	No